The objective of this program is to investigate the mechanisms whereby a particular class of psychotomimetic drugs may affect synaptic transmission and nerve conduction by interfering with or modifying certain physical and chemical properties of excitatory membranes. Interest will center on a group of esters of various heterocyclic iminoalcohols and substituted glycolic acid derivatives, which possess extremely potent psychotomimetic, CNS stimulating, and anticholinergic properties. Among the projects to be undertaken are the following: 1) Investigation of the interfacial interactions of the glycolate esters using monolayers of lipids and proteins as well as lipid bilayers; 2) Investigate the effects of the esters on the binding and release of biogenic amines and ATP utilizing excised bullfrog spinal ganglia and nerve endings isolated from rat brain; 3) Examine the hypothesis that the psychotomimetic potency of the esters is dependent upon the stereochemical configuration of the heterocyclic ring N insofar as it influences the availability of the non-bonded electron pair on N. This latter project will involve the synthesis of two new types of esters and an examination of certain physico-chemical properties which should aid in verifying the stereochemical model. Underlying the biochemical studies is the hypothesis that the esters can 1) substitute for or displace Ca2 ion from neural membranes, and 2) interact with membranous ATP and, thereby, interfere with its presumed functional role of regulating Ca2 ion association-dissociation in the membrane.